Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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In thermally injured patients, inhalation injury is often associated with acute respiratory distress syndrome (ARDS), and is an independent predictor of increased morbidity and mortality. Extracorporeal CO2 removal (ECCO2R) therapy offers new possibilities in protective mechanical ventilation in ARDS patients. We performed an early application of ECCO2R in mild-to-moderate ARDS in sheep ventilated in BiPAP mode. Our aim was to investigate its effect on severity of the lung injury. ⋯ In an ovine model of ARDS due to smoke inhalation and burn injury, early institution of ECCO2R in spontaneously breathing animals was effective in removing CO2 and in reducing PaCO2. However, it had no effect on reducing the severity of lung injury or mortality. Further studies are necessary to detail the interaction between extracorporeal CO2 removal and pulmonary physiology.
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This study evaluated the effects of AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl) phenoxy)decyl) triphenyl phosphonium bromide], a mitochondrially targeted donor of hydrogen sulfide (H2S) in an in vitro model of hypoxia/oxidative stress injury in NRK-49F rat kidney epithelial cells (NRK cells) and in a rat model of renal ischemia-reperfusion injury. Renal oxidative stress was induced by the addition of glucose oxidase, which generates hydrogen peroxide in the culture medium at a constant rate. Glucose oxidase (GOx)-induced oxidative stress led to mitochondrial dysfunction, decreased intracellular ATP content, and, at higher concentrations, increased intracellular oxidant formation (estimated by the fluorescent probe 2, 7-dichlorofluorescein, DCF) and promoted necrosis (estimated by the measurement of lactate dehydrogenase release into the medium) of the NRK cells in vitro. ⋯ The partial protective effects of AP39 correlated with a partial improvement of kidney histological scores and reduced TUNEL staining (an indicator of DNA damage and apoptosis). In summary, the mitochondria-targeted H2S donor AP39 exerted dose-dependent protective effects against renal epithelial cell injury in vitro and renal ischemia-reperfusion injury in vivo. We hypothesize that the beneficial actions of AP39 are related to the reduction of cellular oxidative stress, and subsequent attenuation of various positive feed-forward cycles of inflammatory and oxidative processes.
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Sepsis following hemorrhagic shock is a common clinical condition, in which innate immune system suffers from severe suppression. B and T lymphocyte attenuator (BTLA) is an immune-regulatory coinhibitory receptor expressed not only on adaptive, but also on innate immune cells. Our previous data showed that BTLA gene deficient mice were protected from septic mortality when compared with wild-type control C57BL/6 mice. ⋯ Here, we report that BTLA expression is elevated on innate immune cells after Hem/CLP. However, anti-BTLA antibody treatment increased cytokine (TNF-α, IL-12, IL-10)/chemokine (KC, MIP-2, MCP-1) levels and inflammatory cells (neutrophils, macrophages, dendritic cells) recruitment in the peritoneal cavity, which in turn aggravated organ injury and elevated these animals' mortality in Hem/CLP. When compared with the protective effects of our previous study using BTLA gene deficient mice in a model of lethal septic challenge, we further confirmed BTLA's contribution to enhanced innate cell recruitment, elevated IL-10 levels, and reduced survival, and that engagement of antibody with BTLA potentiates/exacerbates the pathophysiology in Hem/sepsis.
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Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability following Burn Injury.
An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. ⋯ On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn.